Intense interest in the neurotransmitter dopamine stems from the identification of this substance in diverse areas of the mammalian brain, and linkage of dopaminergic systems to a variety of nervous system disorders. Detailed understanding of all aspects of the control of dopamine synthesis, transmission, and reception will enhance our understanding of the normally functioning brain. In addition, it will assist in the treatment of disorders arising from dopamine system dysfunction by increasing our understanding of the mechanisms by which both toxins and therapeutic drugs exert their effects, and aiding in the design of new, more selective drugs. The goal of this project is to develop the gastropod Lymnaea stagnalis as a model system for the study of the electrophysiology and pharmacology of the neurotransmitter dopamine, which is abundant in the brain of this organism. In particular, Lymnaea possess a dopaminergic neuron, the pedal giant, and monosynaptic follower cells which are both large and repeatably identifiable. Preliminary results indicate that the activity of the pedal giant neuron is modulated by application of dopamine, possibly through dopamine autoreceptors. The proposed project is designed to a) determine the ionic bases of the pre and postsynaptic effects of dopamine on identified neurons; b) assess the efficacy of putative dopamine autoreceptor agonists on this system; c) determine the role of dopamine autoreceptors in regulating dopamine synthesis; and d) investigate the role of cAMP in the activation of pre- and postsynaptic dopamine receptor. An ongoing project in our laboratory is the investigation of chronic low-level lead effects on individual neurons. This preliminary study will provide the basis for an investigation of the specific effects of neurotoxins such as lead on the functioning of dopaminergic systems.